Post-traumatic stress disorder (PTSD) is psychiatric disorder, which occurs following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms that can persist for months, years or decades (Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V), and www.behavenet.com/capsules/disorders/ptsd.htm). The diagnosis is principally clinical, based on the fact that something bad happened, and that the patient was there. Behaviorally, the PTSD patient exhibits three defined symptom clusters: (i) hyperarousal (including hypervigilence, irritability, and heightened startle reaction), (ii) avoidance of the condition that was associated with the precipitating event; and (iii) mental re-experiencing of the precipitating event, as if it were actually happening again and again.
There is increasing evidence that there are predisposing genetic risk factors contributing to the development of PTSD. The predisposing deficits are associated behaviorally with hyperarousal, and functionally with increased activity in the amygdala and dorsal anterior cingulate cortex ibid. Evidence from studies with twins suggest that the predisposing deficits are modestly heritable (H), with probabilistic H values of 30-70%. Consistent results have also come from comprehensive studies of soldiers in the Israeli Defense Forces, who were imaged and analyzed before and after front line combat.
The genetic bases of this heritable predisposition are only just beginning to be discerned. Presently, 20 different sequence polymorphisms have been considered as contributing to the predisposing risk factor. Of these, three types of mutations are being principally studied in parallel with functional changes in brains of patients with PTSD. These include (i) catechol-O-methyl transferase; (ii) polymorphisms in the serotonin transporter SLC6A4 gene (viz, the short allele [5HTTLPRs]); and (iii) regulation of glucocorticoid receptor activation by FKBP5 by allele-specific demethylation. However, how these mutations correlate with structural and functional changes in the brain are not known.
The acquired defects following trauma are associated with loss of control on re-experiencing and avoidance behavior. These losses are functionally paralleled by reduced activity in the ventromedial prefrontal cortex (vmPFC, “Area 25”), and reduced activity and volume in the hippocampus. The present thinking is that traumatic experience is responsible for (i) suppressing activity in area 25; (ii) reducing the size of the hippocampus; and (iii) interfering with communication between area 25 and the hippocampus though the connecting entorhinal cortex and uncinate fasciculus.